2l5s - Revision history

OCA at 03:37, 2 October 2022

OCA — Sun, 02 Oct 2022 03:37:48 GMT

←Older revision		Revision as of 03:37, 2 October 2022
Line 1:		Line 1:

	==Solution structure of the extracellular domain of the TGF-beta type I receptor==		==Solution structure of the extracellular domain of the TGF-beta type I receptor==
-	<StructureSection load='2l5s' size='340' side='right'caption='[[2l5s~~]], [[NMR_Ensembles_of_Models \| 10 NMR models~~]]' scene=''>	+	<StructureSection load='2l5s' size='340' side='right'caption='[[2l5s]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2l5s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L5S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2l5s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L5S FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5s OCA], [https://pdbe.org/2l5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l5s RCSB], [https://www.ebi.ac.uk/pdbsum/2l5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5s ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5s OCA], [https://pdbe.org/2l5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l5s RCSB], [https://www.ebi.ac.uk/pdbsum/2l5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5s ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 1A (LDS1A) [MIM:[https://omim.org/entry/609192 609192]]; also known as Furlong syndrome or Loeys-Dietz aortic aneurysm syndrome (LDAS). LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref> <ref>PMID:16596670</ref> <ref>PMID:16791849</ref> <ref>PMID:19883511</ref> <ref>PMID:22113417</ref> Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 2A (LDS2A) [MIM:[https://omim.org/entry/608967 608967]]. An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS2A by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS2A by the OMIM resource. Defects in TGFBR1 are the cause of multiple self-healing squamous epithelioma (MSSE) [MIM:[https://omim.org/entry/132800 132800]]. A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.<ref>PMID:21358634</ref>	+	[https://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN] Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 1A (LDS1A) [MIM:[https://omim.org/entry/609192 609192]; also known as Furlong syndrome or Loeys-Dietz aortic aneurysm syndrome (LDAS). LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref> <ref>PMID:16596670</ref> <ref>PMID:16791849</ref> <ref>PMID:19883511</ref> <ref>PMID:22113417</ref> Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 2A (LDS2A) [MIM:[https://omim.org/entry/608967 608967]. An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS2A by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS2A by the OMIM resource. Defects in TGFBR1 are the cause of multiple self-healing squamous epithelioma (MSSE) [MIM:[https://omim.org/entry/132800 132800]. A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.<ref>PMID:21358634</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.<ref>PMID:7774578</ref> <ref>PMID:8752209</ref> <ref>PMID:8980228</ref> <ref>PMID:9346908</ref> <ref>PMID:15761148</ref> <ref>PMID:16754747</ref> <ref>PMID:18758450</ref>	+	[https://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN] Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.<ref>PMID:7774578</ref> <ref>PMID:8752209</ref> <ref>PMID:8980228</ref> <ref>PMID:9346908</ref> <ref>PMID:15761148</ref> <ref>PMID:16754747</ref> <ref>PMID:18758450</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 22:

	==See Also==		==See Also==
-	*[[TGF-~~ÃÂ²~~ receptor 3D structures\|TGF-~~ÃÂ²~~ receptor 3D structures]]	+	*[[TGF-beta receptor 3D structures\|TGF-beta receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein serine/threonine kinase]]~~	+	[[Category: Hinck C]]
-	[[Category: Hinck, C]]	+	[[Category: Huang T]]
-	[[Category: Huang, T]]	+	[[Category: Ilangovan U]]
-	[[Category: Ilangovan, U]]	+	[[Category: Pardeep M]]
-	[[Category: Pardeep, M]]	+	[[Category: Zuniga JE]]
-	[[Category: Zuniga~~, J E]]~~	+
-	~~[[Category: Alk5]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Transforming growth factor beta]]~~	+
-	~~[[Category: Type i receptor~~]]	+

OCA at 07:37, 14 April 2021

OCA — Wed, 14 Apr 2021 07:37:00 GMT

←Older revision		Revision as of 07:37, 14 April 2021
Line 1:		Line 1:

	==Solution structure of the extracellular domain of the TGF-beta type I receptor==		==Solution structure of the extracellular domain of the TGF-beta type I receptor==
-	<StructureSection load='2l5s' size='340' side='right' caption='[[2l5s]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>	+	<StructureSection load='2l5s' size='340' side='right'caption='[[2l5s]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2l5s]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5S OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2L5S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2l5s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L5S FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR1 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2l5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5s OCA], [~~http~~://pdbe.org/2l5s PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2l5s RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2l5s PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5s ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5s OCA], [https://pdbe.org/2l5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l5s RCSB], [https://www.ebi.ac.uk/pdbsum/2l5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5s ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 1A (LDS1A) [MIM:[~~http~~://omim.org/entry/609192 609192]]; also known as Furlong syndrome or Loeys-Dietz aortic aneurysm syndrome (LDAS). LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref> <ref>PMID:16596670</ref> <ref>PMID:16791849</ref> <ref>PMID:19883511</ref> <ref>PMID:22113417</ref> Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 2A (LDS2A) [MIM:[~~http~~://omim.org/entry/608967 608967]]. An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS2A by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS2A by the OMIM resource. Defects in TGFBR1 are the cause of multiple self-healing squamous epithelioma (MSSE) [MIM:[~~http~~://omim.org/entry/132800 132800]]. A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.<ref>PMID:21358634</ref>	+	[[https://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 1A (LDS1A) [MIM:[https://omim.org/entry/609192 609192]]; also known as Furlong syndrome or Loeys-Dietz aortic aneurysm syndrome (LDAS). LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref> <ref>PMID:16596670</ref> <ref>PMID:16791849</ref> <ref>PMID:19883511</ref> <ref>PMID:22113417</ref> Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 2A (LDS2A) [MIM:[https://omim.org/entry/608967 608967]]. An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS2A by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS2A by the OMIM resource. Defects in TGFBR1 are the cause of multiple self-healing squamous epithelioma (MSSE) [MIM:[https://omim.org/entry/132800 132800]]. A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.<ref>PMID:21358634</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.<ref>PMID:7774578</ref> <ref>PMID:8752209</ref> <ref>PMID:8980228</ref> <ref>PMID:9346908</ref> <ref>PMID:15761148</ref> <ref>PMID:16754747</ref> <ref>PMID:18758450</ref>	+	[[https://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.<ref>PMID:7774578</ref> <ref>PMID:8752209</ref> <ref>PMID:8980228</ref> <ref>PMID:9346908</ref> <ref>PMID:15761148</ref> <ref>PMID:16754747</ref> <ref>PMID:18758450</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 24:

	==See Also==		==See Also==
-	*[[TGF-~~beta~~ receptor\|TGF-~~beta~~ receptor]]	+	*[[TGF-ÃÂ² receptor 3D structures\|TGF-ÃÂ² receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 30:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]
	[[Category: Hinck, C]]		[[Category: Hinck, C]]

OCA at 19:44, 1 August 2018

OCA — Wed, 01 Aug 2018 19:44:34 GMT

←Older revision		Revision as of 19:44, 1 August 2018
Line 1:		Line 1:
		+
	==Solution structure of the extracellular domain of the TGF-beta type I receptor==		==Solution structure of the extracellular domain of the TGF-beta type I receptor==
	<StructureSection load='2l5s' size='340' side='right' caption='[[2l5s]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='2l5s' size='340' side='right' caption='[[2l5s]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
Line 6:		Line 7:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5s OCA], [http://pdbe.org/2l5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l5s RCSB], [http://www.ebi.ac.uk/pdbsum/2l5s PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5s OCA], [http://pdbe.org/2l5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l5s RCSB], [http://www.ebi.ac.uk/pdbsum/2l5s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5s ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 01:50, 11 September 2015

OCA — Fri, 11 Sep 2015 01:50:56 GMT

←Older revision		Revision as of 01:50, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2l5s' size='340' side='right' caption='[[2l5s]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='2l5s' size='340' side='right' caption='[[2l5s]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2l5s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L5S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2l5s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L5S FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2l5s RCSB], [http://www.ebi.ac.uk/pdbsum/2l5s PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5s OCA], [http://pdbe.org/2l5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l5s RCSB], [http://www.ebi.ac.uk/pdbsum/2l5s PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2l5s" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[TGF-beta receptor\|TGF-beta receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]
	[[Category: Hinck, C]]		[[Category: Hinck, C]]

OCA at 12:15, 18 December 2014

OCA — Thu, 18 Dec 2014 12:15:07 GMT

←Older revision		Revision as of 12:15, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2l5s~~\| ~~PDB~~=2l5s \| ~~SCENE~~= }}	+	==Solution structure of the extracellular domain of the TGF-beta type I receptor==
-	===~~Solution~~ structure of the extracellular domain of the TGF-beta type I receptor~~===~~	+	<StructureSection load='2l5s' size='340' side='right' caption='[[2l5s]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_21821041}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2l5s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L5S FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TGFBR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2l5s RCSB], [http://www.ebi.ac.uk/pdbsum/2l5s PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 1A (LDS1A) [MIM:[http://omim.org/entry/609192 609192]]; also known as Furlong syndrome or Loeys-Dietz aortic aneurysm syndrome (LDAS). LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref> <ref>PMID:16596670</ref> <ref>PMID:16791849</ref> <ref>PMID:19883511</ref> <ref>PMID:22113417</ref> Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 2A (LDS2A) [MIM:[http://omim.org/entry/608967 608967]]. An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS2A by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS2A by the OMIM resource. Defects in TGFBR1 are the cause of multiple self-healing squamous epithelioma (MSSE) [MIM:[http://omim.org/entry/132800 132800]]. A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.<ref>PMID:21358634</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.<ref>PMID:7774578</ref> <ref>PMID:8752209</ref> <ref>PMID:8980228</ref> <ref>PMID:9346908</ref> <ref>PMID:15761148</ref> <ref>PMID:16754747</ref> <ref>PMID:18758450</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Transforming growth factor beta isoforms (TGF-beta) are among the most recently evolved members of a signaling superfamily with more than 30 members. TGF-beta play vital roles in regulating cellular growth and differentiation, and they signal through a highly restricted subset of receptors known as TGF-beta type I receptor (TbetaR-I) and TGF-beta type II receptor (TbetaR-II). TGF-beta's specificity for TbetaR-I has been proposed to arise from its pre-helix extension, a five-residue loop that binds in the cleft between TGF-beta and TbetaR-II. The structure and backbone dynamics of the unbound form of the TbetaR-I extracellular domain were determined using NMR to investigate the extension's role in binding. This showed that the unbound form is highly similar to the bound form in terms of both the beta-strand framework that defines the three-finger toxin fold and the extension and its characteristic cis-Ile54-Pro55 peptide bond. The NMR data further showed that the extension and two flanking 3(10) helices are rigid on the nanosecond-to-picosecond timescale. The functional significance of several residues within the extension was investigated by binding studies and reporter gene assays in cultured epithelial cells. These demonstrated that the pre-helix extension is essential for binding, with Pro55 and Pro59 each playing a major role. These findings suggest that the pre-helix extension and its flanking prolines evolved to endow the TGF-beta signaling complex with its unique specificity, departing from the ancestral promiscuity of the bone morphogenetic protein subfamily, where the binding interface of the type I receptor is highly flexible.

-	~~==Disease==~~	+	The TbetaR-I pre-helix extension is structurally ordered in the unbound form and its flanking prolines are essential for binding.,Zuniga JE, Ilangovan U, Mahlawat P, Hinck CS, Huang T, Groppe JC, McEwen DG, Hinck AP J Mol Biol. 2011 Sep 30;412(4):601-18. Epub 2011 Jul 29. PMID:21821041<ref>PMID:21821041</ref>
-	~~[[http://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Defects in TGFBR1 are the cause of Loeys~~-~~Dietz syndrome type 1A (LDS1A) [MIM:[http://omim.org/entry/609192 609192]]; also known as Furlong syndrome or Loeys~~-~~Dietz aortic aneurysm syndrome (LDAS). LDS1~~ is ~~an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity~~ and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref><ref>PMID:16596670</ref><ref>PMID:16791849</ref><ref>PMID:19883511</ref><ref>PMID:22113417</ref> Defects in TGFBR1 are ~~the cause of Loeys-Dietz syndrome type 2A (LDS2A) [MIM:[http://omim.org/entry/608967 608967]]. An aortic aneurysm syndrome with widespread systemic involvement~~. ~~Physical findings include prominent joint laxity~~, ~~easy bruising~~, ~~wide and atrophic scars~~, ~~velvety and translucent skin with easily visible veins~~, ~~spontaneous rupture of the spleen or bowel~~, ~~diffuse arterial aneurysms and dissections~~, ~~and catastrophic complications of pregnancy~~, ~~including rupture of the gravid uterus and the arteries~~, ~~either during pregnancy or in the immediate postpartum period~~. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (~~TAAD~~) ~~(PubMed~~:~~16791849)~~. ~~This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS2A by having aneurysms restricted to thoracic aorta~~. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS2A by the OMIM resource. Defects in TGFBR1 are the cause of multiple self-healing squamous epithelioma (MSSE) [MIM:[http://omim.org/entry/132800 132800]]. A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.<ref>PMID:~~21358634~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor~~, ~~TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating~~ a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the ~~receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2~~. ~~Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4~~. ~~The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription~~ of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.<~~ref~~>~~PMID:7774578~~</~~ref~~>~~<ref>PMID:8752209</ref><ref>PMID:8980228</ref><ref>PMID:9346908</ref><ref>PMID:15761148</ref><ref>PMID:16754747</ref><ref>PMID:18758450</ref>~~	+	</div>
-		+	== References ==
-	==~~About this Structure==~~	+	<references/>
-	[[2l5s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5S OCA].	+	__TOC__
-		+	</StructureSection>
-	~~==Reference~~==	+
-	~~<ref group="xtra">PMID:021821041</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]
-	[[Category: Hinck, C.]]	+	[[Category: Hinck, C]]
-	[[Category: Huang, T.]]	+	[[Category: Huang, T]]
-	[[Category: Ilangovan, U.]]	+	[[Category: Ilangovan, U]]
-	[[Category: Pardeep, M.]]	+	[[Category: Pardeep, M]]
-	[[Category: Zuniga, J E.]]	+	[[Category: Zuniga, J E]]
	[[Category: Alk5]]		[[Category: Alk5]]
	[[Category: Signaling protein]]		[[Category: Signaling protein]]
	[[Category: Transforming growth factor beta]]		[[Category: Transforming growth factor beta]]
	[[Category: Type i receptor]]		[[Category: Type i receptor]]

OCA at 18:40, 24 March 2013

OCA — Sun, 24 Mar 2013 18:40:34 GMT

←Older revision		Revision as of 18:40, 24 March 2013
Line 1:		Line 1:
-	[[Image:2l5s.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_2l5s", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_2l5s\| PDB=2l5s \| SCENE= }}		{{STRUCTURE_2l5s\| PDB=2l5s \| SCENE= }}
-
	===Solution structure of the extracellular domain of the TGF-beta type I receptor===		===Solution structure of the extracellular domain of the TGF-beta type I receptor===
		+	{{ABSTRACT_PUBMED_21821041}}

		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 1A (LDS1A) [MIM:[http://omim.org/entry/609192 609192]]; also known as Furlong syndrome or Loeys-Dietz aortic aneurysm syndrome (LDAS). LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.<ref>PMID:15731757</ref><ref>PMID:16596670</ref><ref>PMID:16791849</ref><ref>PMID:19883511</ref><ref>PMID:22113417</ref> Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 2A (LDS2A) [MIM:[http://omim.org/entry/608967 608967]]. An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS2A by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS2A by the OMIM resource. Defects in TGFBR1 are the cause of multiple self-healing squamous epithelioma (MSSE) [MIM:[http://omim.org/entry/132800 132800]]. A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.<ref>PMID:21358634</ref>

-	~~<!--~~	+	==Function==
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21821041}}, adds the Publication Abstract to the page~~	+	[[http://www.uniprot.org/uniprot/TGFR1_HUMAN TGFR1_HUMAN]] Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.<ref>PMID:7774578</ref><ref>PMID:8752209</ref><ref>PMID:8980228</ref><ref>PMID:9346908</ref><ref>PMID:15761148</ref><ref>PMID:16754747</ref><ref>PMID:18758450</ref>
-	~~(as it appears on PubMed at~~ http://www.~~pubmed~~.~~gov)~~, ~~where 21821041~~ is the ~~PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_21821041}}~~	+

	==About this Structure==		==About this Structure==
Line 22:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021821041</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021821041</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein serine/threonine kinase]]		[[Category: Receptor protein serine/threonine kinase]]

OCA: Protected "2l5s" [edit=sysop:move=sysop]

OCA — Sun, 30 Oct 2011 09:16:53 GMT

Protected "2l5s" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:16, 30 October 2011

OCA at 09:16, 30 October 2011

OCA — Sun, 30 Oct 2011 09:16:45 GMT

←Older revision		Revision as of 09:16, 30 October 2011
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-	~~'''Unreleased structure'''~~	+	[[Image:2l5s.png\|left\|200px]]

-	The ~~entry 2l5s~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_2l5s", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_2l5s\| PDB=2l5s \| SCENE= }}

-	~~Authors: Zuniga, J.E., Ilangovan, U., Pardeep, M., Hinck, C., Huang, T.~~	+	===Solution structure of the extracellular domain of the TGF-beta type I receptor===

-	Description: Solution structure of the extracellular domain of the TGF-beta type I receptor

-	~~''Page seeded by~~ [http://oca.weizmann.ac.il/oca OCA ] ~~on Wed Nov 24 13~~:49:~~27 2010''~~	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21821041}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21821041 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21821041}}
		+
		+	==About this Structure==
		+	[[2l5s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5S OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021821041</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Receptor protein serine/threonine kinase]]
		+	[[Category: Hinck, C.]]
		+	[[Category: Huang, T.]]
		+	[[Category: Ilangovan, U.]]
		+	[[Category: Pardeep, M.]]
		+	[[Category: Zuniga, J E.]]
		+	[[Category: Alk5]]
		+	[[Category: Signaling protein]]
		+	[[Category: Transforming growth factor beta]]
		+	[[Category: Type i receptor]]

OCA at 10:37, 24 November 2010

OCA — Wed, 24 Nov 2010 10:37:56 GMT

←Older revision		Revision as of 10:37, 24 November 2010
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 2l5s is ON HOLD	+	The entry 2l5s is ON HOLD until Paper Publication

	Authors: Zuniga, J.E., Ilangovan, U., Pardeep, M., Hinck, C., Huang, T.		Authors: Zuniga, J.E., Ilangovan, U., Pardeep, M., Hinck, C., Huang, T.
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	Description: Solution structure of the extracellular domain of the TGF-beta type I receptor		Description: Solution structure of the extracellular domain of the TGF-beta type I receptor

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu~~ Nov ~~18 00~~:25:35 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 24 13:49:27 2010''

OCA at 21:14, 17 November 2010

OCA — Wed, 17 Nov 2010 21:14:21 GMT

←Older revision		Revision as of 21:14, 17 November 2010
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	The entry 2l5s is ON HOLD		The entry 2l5s is ON HOLD

-	Authors: Zuniga, J.E.	+	Authors: Zuniga, J.E., Ilangovan, U., Pardeep, M., Hinck, C., Huang, T.

	Description: Solution structure of the extracellular domain of the TGF-beta type I receptor		Description: Solution structure of the extracellular domain of the TGF-beta type I receptor

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed~~ Nov ~~10 06~~:23:58 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Nov 18 00:25:35 2010''